Current theoretical models of nicotine addiction assume a relatively close relationship between the intensity and duration of nicotine use and the development of nicotine dependence. However, this relationship is weaker than one might expect; use measures typically account for only a small portion of the variance in dependence. Furthermore, many long-time, heavy daily smokers fail to meet DSM- IV dependence criteria. The weak relationship between use and dependence may result from inadequate or insensitive measures of dependence, adequately characterizations of nicotine exposure, and/or relative resistance to becoming nicotine dependent in some heavy cigarette users. The purpose of this application is to utilize established human laboratory procedures to rigorously assess the possibility that a subpopulation of smokers may be relatively resistant to becoming nicotine dependent despite extensive nicotine use. The specific aims are: 1) To determine whether individuals who fail to meet DSM-IV criteria for nicotine dependence also exhibit lower dependence according to other self-report measures; 2) To determine whether use/exposure characteristics not assessed in epidemiological measures of smoking behavior can account for individual differences in nicotine dependence; 3) To determine whether differences in self-report measures of dependence predict who will be able to refrain from smoking when given an incentive to do so among individuals with similar nicotine use histories. In the proposed study, we will recruit individuals who vary along both current use (5-10 versus 20+ cigarettes/day) and DSM-IV dependence (dependent versus non- dependent) criteria in a 2 x 2 design. We predict that individuals failing to meet criteria for DSM-IV nicotine dependence will demonstrate relative low levels of dependence is assessed by other continuous, multidimensional measures, and that these differences will not be fully explained by nicotine use/exposure. Furthermore, we expect individuals failing to meet DSM-IV dependence to be more capable of refraining from cigarette use in an abstinence test than DSM-IV dependent smokers. These findings would suggest that individual differences in DSM-IV dependence that arise in smokers with comparable nicotine use represent real differences in vulnerability to developing nicotine dependence that deserve further research. The proposed study will determine whether some regular, prolonged smokers are relatively resistant to becoming nicotine dependent. If such a subpopulation is identified, future studies will address what factors may be necessary for nicotine dependence to develop or, conversely, what factors might protect some individuals from becoming highly dependent. Identifying the mechanisms which account for individual differences in nicotine dependence may highlight novel approaches to both prevention and treatment of nicotine addiction. [unreadable] [unreadable] [unreadable]